## The First Committed Step of β-Oxidation ### Enzyme Identity **Acyl-CoA dehydrogenase** catalyzes the first oxidation step in the β-oxidation cycle, introducing a double bond between the α and β carbons of the acyl-CoA molecule. ### Why This Is the "First Committed" Step **Key Point:** Acyl-CoA synthetase (also called fatty acyl-CoA ligase) activates free fatty acids to acyl-CoA in the cytoplasm or ER — this is an activation step, not part of the β-oxidation cycle proper. Once activated, the acyl-CoA enters mitochondria via the carnitine shuttle and undergoes β-oxidation. **High-Yield:** The four enzymes of each β-oxidation cycle are: 1. **Acyl-CoA dehydrogenase** — oxidation (FAD → FADH~2~) 2. **Enoyl-CoA hydratase** — hydration 3. **3-hydroxyacyl-CoA dehydrogenase** — oxidation (NAD^+^ → NADH) 4. **3-ketoacyl-CoA thiolase** — thiolysis (releases acetyl-CoA) ### Cofactor and Regulation - Acyl-CoA dehydrogenase uses **FAD** as the electron acceptor, generating FADH~2~. - This enzyme is inhibited by its product, acetyl-CoA, and by NADH/NAD^+^ ratio — a key feedback mechanism. - Different chain-length-specific isoforms exist: short-chain (SCAD), medium-chain (MCAD), long-chain (LCAD), and very-long-chain (VLCAD) acyl-CoA dehydrogenases. **Clinical Pearl:** MCAD deficiency is the most common fatty acid oxidation disorder, presenting with hypoketotic hypoglycemia during fasting or illness.
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